The human ribosomal gene (rDNA) is a 44 kb unit that forms tandemly repeated complexes on each of the five pairs of acrocentric chromosomes and are collectively known as nucleolar organizing regions (NORs). Based on knowledge of the molecular details of this unit and of other acrocentric short arm DNAs, research using the tools of molecular biology, cytogenetics, confocal laser scanning and electron microscopy now aims (1) to resolve the molecular topography of the nucleolus, (2) to characterize the DNA between silver-staining regions of dNORs in order to reveal the mechanism of double NOR (dNOR) formation, and (3): to understand the role that nucleolar and other specific DNA sequences have in acrocentric and sex chromosome non-disjunction events which lead to birth defects. Our hypothesis is that nucleolus formation provides a nuclear compartment where the physicochemical properties of sequences on the acrocentric short arm promote normal concerted evolution and foster aberrant translocation and nondisjunction events among themselves and nearby sex chromosomes. Our long term goal is to determine the sequences and protein activities that are important in these processes. Moreover, use of the complete nucleotide sequence of a representative rDNA unit will permit further investigations concerning the details of the gene's expression, variation, evolution, and flanking DNA. Specifically, it will be determined if transcription occurs in the human intergenic spacer (IGS) and whether a particular IGS segment regulates gene expression. Various sequences within genes derived from homologous and non-homologous acrocentric chromosomes will be compared. The physical map and sequence comparisons between the spacers of different primate species will elucidate recent events in the formation of this portion of the gene. DNA nucleotide sequences surrounding the distal and proximal junction regions from different acrocentric chromosomes will permit conclusions concerning the extent of recombinations occurring on short arms of acrocentric chromosomes.